1. Field of the Invention
The present invention relates to a process for enantioselective preparation of (S)-Clopidogrel, a potent platelet aggregation inhibitor, and related compounds. More particularly, the present invention relates to a process for the preparation of (S)-Clopidogrel in high enantioselectivity and yield. (S)-Clopidogrel is used as an antithrombotic agent for treatment of patients with vascular diseases, myocardial infraction and stroke.
2. Description of the Prior Art
Currently there are two known processes for the preparation of (S)-Clopidogrel. Each of these processes relies on classical resolution or enzymatic techniques to introduce the sole chiral center into the molecule.
U.S. Pat. No. 4,847,265 describes a method of preparation of Clopidogrel employing classical resolution techniques.
French Patent Applications Nos. 2,530,247 and 2,769,313 describe commercial methods that are currently used to synthesize Clopidogrel.
When classical resolution techniques are employed, the following problems must be overcome: (1) a suitable resolving agent must be found; (2) the resolving reagent must be recycled to make the resolution economical; and (3) isolation and racemization of the starting material from the mother liquor must be carried out efficiently to improve the economics and overall yield.
The problems with enzymatic resolution techniques are similar to classical resolution techniques in that low yield of the desired enantiomer makes it necessary to isolate and racemize starting material from the mother liquor. An added problem with enzymatic resolution is low volumetric throughput and tedious work up procedures.
To overcome these disadvantages of the prior art, laborious procedures and separations would be required to either enrich the racemic product in one or the other enantiomer or to efficiently and completely separate one enantiomer from the other.
The present invention employs a novel approach, which does not require enzymatic or classical resolution techniques to obtain a final product having high enantioselectivity (ee).
In addition, the present invention overcomes the disadvantages of the prior art described above by providing a process, which enables one to obtain an enantiomerically pure or enantiomerically enriched product without the need for laborious procedures and separations.